Technical Field
The present invention relates to gold(I) complexes with anticancer or antitumor properties. More specifically, these gold(I) complexes can be either mono- or binuclear and each gold atom is coordinated to mixed ligands having different functional groups.
Description of the Related Art
The “background” description provided herein is for the purpose of generally presenting the context of the disclosure. Work of the presently named inventors, to the extent it is described in this background section, as well as aspects of the description which may not otherwise qualify as prior art at the time of filing, are neither expressly or impliedly admitted as prior art against the present invention.
The use of cisplatin and its analogues such as oxaliplatin and carboplatin as metal-based anticancer drugs is well acknowledged in the field of chemotherapy [B. Rosenberg, L. Van Camp and T. Krigas, Nature, 205 (1965) 698; N. Cutillas, G. S. Yellol, C. de Haro, C. Vicente, V. Rodriguez and J. Ruiz, Coord. Chem. Rev., 257 (2013) 2784; Ž. D. Bugarčić, J. Bogojeski, B. Petrović, S. Hochreuther and R. Van Eldik, Dalton. Trans., 41 (2012) 12329; C. Vetter, C. Wagner, J. Schmidt and D. Steinborn, Inorg. Chim. Acta, 359 (2006) 4326; A. Casini and L. Messori, Curr. Top. Med. Chem. 11 (2011) 2647; E. Márta Nagy, L. Ronconi, C. Nardon and D. Fregona, Mini-Reviews in Med. Chem., 12 (2012) 1216—each incorporated herein by reference in its entirety]. These drugs have been used for the treatment of cancer patients worldwide. However, it is also known that cisplatin and its analogues have serious side effects, such as oto-, neuro-, and nephrotoxicity, which decrease its effectiveness in cancer therapy [S. Ahmad, A. A. Isab and S. Ali, Tradition Met. Chem., 31 (2006) 1003; S. R. McWhinney, R. M. Goldberg and H. L. McLeod, Mol. Cancer Ther., 8 (2009) 10; W. Liu and R. Gust, Chem. Soc. Rev. 42 (2013) 755; X. Yao, K. Panichpisal, N. Kurtzman, and K. Nugent, Am. J. Mod. Sci., 334 (2007) 115—each incorporated herein by reference in its entirety]. Consequently, gold(I) and gold(III) complexes had been investigated as non-platinum based anticancer candidates [S. S. Al-Jaroudi, M. Monim-ul-Mehboob, M. Altaf, M. Fettouhi, M. I. M. Wazeer, S. Altuwaijri and A. A. Isab, New J. Chem., (2014), DOI:10:1039/c3nj01624b; S. M. Janković, A. Djeković, Ž. D. Bugarčić, S. V. Janković, G. Lukić, M. Folic and D. Čanović, Biometals, 25 (2012) 919; S. S. Al-Jaroudi, M. I. M. Wazeer, A. A. Isab and S. Altuwaijri, Polyhedron, 50 (2013) 434; R. B. Bostancioglu, K. Isik, H. Gene, K. Benkli and A. T. Koparal, J. Med. Chem., 27 (2012) 458—each incorporated herein by reference in its entirety].
The study of gold complexes, bearing different functional ligands exhibiting physical, chemical, biological and pharmacological properties, has gained much attention [S. S. Al-Jaroudi, M. Monim-ul-Mehboob, M. Altaf, M. Fettouhi, M. I. M. Wazeer, S. Altuwaijri and A. A. Isab, New J. Chem., (2014), DOI:10:1039/c3nj01624b; S. M. Janković, A. Djeković, Ž. D. Bugarčić, S. V. Janković, G. Lukić, M. Folic and D. Čanović, Biometals, 25 (2012) 919; S. S. Al-Jaroudi, M. I. M. Wazeer, A. A. Isab and S. Altuwaijri, Polyhedron, 50 (2013) 434; R. B. Bostancioglu, K. Isik, VI. Gene, K. Benkli and A. T. Koparal, J. Med. Chem., 27 (2012) 458—each incorporated herein by reference in its entirety]. The gold(I) complexes have been studied as anti-arthritic and anti-microbial agents [O. Crespo, V. V. Brusko, M. C. Giameno, M. L. Tornil, A. Laguna and N. G. Zabirov, Eur. J. Inorg. Chem., (2004) 423; K. Nomiya, R. Noghochi and M. Oda, Inorg. Chim. Acta. 298 (2000) 24; H.-Q. Liu, T.-C. Cheung, S.-M. Peng and C.-M. Che, J. Chem. Soc., Chem. Comm., (1995) 1787; C. J. O'Connor and E. Sinn, Inorg. Chem., 17 (1978) 2067; M. A. Cinellu, G. Minghetti, M. V. Pinna, S. Stoccoro, A. Zucca, and M. Manassero, J. Chem. Soc., Dalton Trans., (1998) 1735—each incorporated herein by reference in its entirety]. For instance, the drugs like Auranofin, Solganol and Myocrisin have frequently been used for the treatment of rheumatoid arthritis [S. H. van Rijt and P. J. Sadler, Drug Discovery Today, 14 (2009) 1089; R. Noghuchi, A. Hara, A. Sugie and K. Nomiya, Inorg. Chem. Comm., 9 (2006) 355; K. Nomiya, R. Noghuchi, K. Ohsawa, K. Tsuda and M. Oda, J. Inorg. Biochem., 78 (2000) 363; B. P. Howe, Met.-Based Drugs., 4 (1997) 273; J. Ctalano and A. O. Etogo, J. Organomet. Chem., 690 (2005) 6041—each incorporated herein by reference in its entirety]. Interesting, the extensive cell-based (in vitro) and animal (in vivo) studies have revealed the potent anti-cancer activities of diverse classes of gold(I) and gold(III) complexes with a wide range of ligands against a panel of human cancer cell lines [J. C. Lima and L. Rodriguez, J. Med. Chem., 11 (2011) 921; C-M Che and R. W-Y. Sun, Chem. Commun., 47 (2011) 9554; P. Calami, A. Carotti, T. Guerri, L. Messori, E. Mini, P. Orioli and G. P. Speroni, J. Inorg. Biochem., 66 (1997) 103—each incorporated herein by reference in its entirety].
Bridged di-gold(I) complexes existing in a linear 2-coordinate configuration like [ClAu(P—P)AuCl] where P—P is a bisphosphine), tend to be more effective than free ligands and such complexes also lend to exhibit a broad range of anticancer activity [R. K. Johnson, C. K. Mirabelli, L. F. Faucette, F. L. McCabe, B. M. Sutton, D. L. Bryan, G. R. Girard and D. T. Hill, Proc. Amer. Assoc. Cancer Res., 26 (1985) 254; C. K. Mirabelli, L. F. Faucette, F. L. McCabe, B. M. Sutton, D. L. Bryan, G. R. Girard, D. T. Hill, J. O. Bartus, S. T. Crooke and R. K. Johnson, J. Med. Chem., 30 (1987) 2181—each incorporated herein by reference in its entirety]. This has inspired the synthesis of stable 4-coordinate digold(I) diphosphine complexes [S. J. Berners-Price, M. A. Mazid and P. J. Sadler, J. Chem. Soc., Dalton Trans., (1984) 969; S. J. Berners-Price and P. J. Sadler, Inorg. Chem., 25 (1986) 3822; D. T. Hill, G. R. Girard, U.S. Pat. No. 4,755,611, July 1988—each incorporated herein by reference in its entirety]. The effect of structural variation in chelated bis(diphosphate) gold(I) complexes [Au(R2P(CH2)nPR2)]X on their cytotoxicity and activity against P388 leukaemia, B16 melanoma and M5076 reticulum cell sarcoma has been studied [G. F. Rush, D. W. Albers, P. Meunies, K. Leffler, P. F. Smith, Toxicologist, 7 (1987) 59—incorporated herein by reference in its entirety]. J. W. Faamaua et al. reported compounds of general formula [(Ph2P(CH2)nPPh2)(AuS2CNR2)2], n=1, 2 or 3 and R=Et or c-hexyl [J. W. Faamaua and E. R. T. Tiekinka, J. Coord. Chem., 31(2) (1994) 93—incorporated herein by reference in its entirety].
Since the first decade of 21st century, a new class of gold complexes with dithiocarbamate ligands has emerged as anticancer agents. In this regard, Fregona and coworkers synthesized and characterized some novel gold(III) compounds containing N,N-dimethyldithiocarbamate and ethyl sarcosine dithiocarbamate exhibiting potential chemical and biological profile [L. Ronconi, L. Giovagnini, C. Marzano, F. Bettio, R. Graziani, G. Pilloni, and D. Fregona, Inorg. Chem., 44 (2005) 1867—incorporated herein by reference in its entirety]. Dibromo(N,N-dimethyldithiocarbamato)gold(III) also showed a noteworthy inhibition of in-vivo MDA-MB-231 breast cancer growth [V. Milacic, D. Chen, L. Ronconi, K. R. Landis-Piwowar, D. Fregona and Q. P. Dou, Cancer Res., 66 (2006) 10478—incorporated herein by reference in its entirety]. Zhang et al. reported that gold(I)-dithiocarbamato species, namely [Au(ESDT)](2) could hamper the chymotrypsin-like activity of purified 20S proteasome and 26S proteasome in human breast cancer MDA-MB-231 cells, resulting in accumulation of ubiquitinated proteins and proteasome target proteins, and induction of cell death [X. Zhang, M. Frezza, V. Milacic, L. Ronconi, Y. Fan, C. Bi, D. Fregona and Q. P. Dou, J. Cell Biochem., 109 (2010) 162—incorporated herein by reference in its entirety]. Recently, the modern research has progressively targeted in search of new gold(I) complexes as potential anticancer drugs [S. Ahmad, A. A. Isab, S. Ali and A. R. Al-Arfaj, Polyhedron, 25 (2006) 1633; D. V. Partyka, T. J. Robilotto, M. Zeller, A. D. Hunter, T. G. Gray, Proc. Natl. Acad. Sci., (USA) 105 (2008) 14293; V. Wang, Q.-Y. He and C.-M. Che, J.-F. Chiu, Proteomics, 6 (2006) 131; Y. Shi, W. Chu, V. Wang, S. Wang, J. Du, J. Zhang, S. Li, G. Zhou, X. Qin and C. Zhang, Inorg. Chem. Comm., 30 (2013) 178; M. Monim-ul-Mehboob, M. Altaf, M. Fettouhi, A. A. Isab, M. I. M. Wazeer, M. N. Shaikh and S. Altuwaijri, Polyhedron, 61 (2003) 225—each incorporated herein by reference in its entirety].
Lung and colorectal cancers are frequent causes of cancer-related death in both males and females while cervix cancer is responsible for cancer deaths in females exclusively. Hence, there remains an unmet, dire need of new drugs to treat such lethal diseases through chemotherapy.